Risk prediction of iron deficiency for plasmapheresis donors in China: Development and validation of a prediction model.

BACKGROUND AND OBJECTIVES: The present study aims to evaluate the iron stores in plasmapheresis donors and develop and validate an iron deficiency (ID) risk prediction model for plasmapheresis donors with potential or existing ID. MATERIALS AND METHODS: We assessed plasmapheresis donors' serum ferritin (SF) and haemoglobin (Hb) levels. The candidate factors showing significant differences in the multivariate logistic regression analysis were used to establish a risk prediction scoring system. The participants were divided into a training cohort and an internal validation cohort in a 7:3 ratio. Additional plasmapheresis donors from a different station were recruited for external validation. RESULTS: The SF levels in both male and female donors in the high-frequency group were significantly lower than those of new donors (male: p < 0.001; female: p = 0.008). The prevalence of ID in female regular donors with a high frequency was significantly higher than that in new donors (33.1% vs. 24.6%; odds ratio = 1.209 [95% CI: 1.035-1.412]). Donation frequency, age, Hb, body mass index and being pre-menopausal were identified as independent risk factors for ID (p < 0.05). The developed model exhibited good discrimination ability (area under the receiver operating characteristic curve >0.7) and calibration (p > 0.05) in development, internal validation cohorts and external validation cohorts. CONCLUSION: A higher donation frequency has been associated with reduced SF levels and an increased risk of ID in women. The developed ID risk prediction model demonstrates moderate discriminative power and good model fitting, suggesting its potential clinical utility.

Development and validation of a nomogram for predicting the risk of vasovagal reactions after plasma donation.

BACKGROUND AND OBJECTIVES: Vasovagal reactions (VVRs) are the most common adverse reactions and are frequently associated with serious donor adverse events. Even mild VVRs can lead to a significant reduction in the likelihood of subsequent donations. The purpose of this study is to explore the factors related to the occurrence of VVRs after plasma donation and to construct a nomogram to identify individuals at risk for VVRs to improve the safety of plasma donors. MATERIALS AND METHODS: We collected the donation data from July 2019 to June 2020 from a plasma center in Sichuan, China, to explore the independent risk factors for vasovagal reactions. From these data, we constructed and validated a predictive model for vasovagal reactions. RESULTS: VVRs after plasma donation occurred 737 times in 120 448 plasma donations (0.66%). Gender, season, donor status, weight, pulse, duration of donation, and cycle were independent risk factors for VVRs (P< 0.05). The concordance index (C-index) of a logistic model in the derivation cohort was 0.916, with a Hosmer-Lemeshow goodness-of-fit probability of 0.795. The C-index of a logistic model in the validation cohort was 0.916, with a Hosmer-Lemeshow goodness-of-fit probability of 0.224. The calibration curve showed that the predicted results were in good agreement with the actual observed results. CONCLUSION: This study preliminarily constructed and verified a prediction model for VVRs after plasma donation. The model nomogram is practical and can identify high-risk donors.

Differential expression of exosomal microRNAs in fresh and senescent apheresis platelet concentrates.

Patients have a high risk of suffering adverse reactions after receiving platelet products stored for 5 days. Bioactive exosomes in platelet products can be accumulated during storage, which is associated with adverse reactions. MicroRNAs are one of the critical cargoes in exosomes, which participate in cell differentiation, metabolism, and immunomodulation. This study intends to elucidate and analyze the differential expression of exosomal microRNAs in apheresis platelet concentrates during storage and predict the potential functions of target genes. Apheresis platelet concentrates were used to isolate exosomes by ultracentrifugation. Exosomes were phenotyped by western blot, transmission electron microscopy, and nano flow cytometry. The differential expression of the exosomal microRNAs was obtained by a microarray test using four bags of apheresis platelets stored for 5 days compared with 1 day. The differentially expressed microRNAs between the two time points were identified, and their target genes were analyzed by miRWalk and miRDB. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the target genes' functions. Fifteen bags of apheresis platelet concentrates stored for 1 day and 5 days were used to verify the microarray results by quantitative reverse transcription-polymerase chain reactions (qRT-PCR). There were 134 microRNAs in total expressed differently in the two groups (day 1 and day 5), with 57 microRNAs up-regulated and 77 down-regulated (|fold change| > 2.0 and P < .05). Thirteen up-regulated microRNAs (hsa-miR-22-3p, hsa-miR-223-3p, hsa-miR-21-5p, hsa-miR-23a-3p, hsa-miR-320b, hsa-let-7a-5p, hsa-miR-25-3p, hsa-miR-126-3p, hsa-miR-320c, hsa-miR-342-3p, hsa-miR-320d, hsa-miR-328-3p, and hsa-miR-320e) detected in all samples were selected to validate the results. The qRT-PCR results showed that five (hsa-miR-22-3p, hsa-miR-223-3p, hsa-miR-21-5p, hsa-miR-23a-3p, and hsa-miR-320b) of them were increased more than 10-fold (P < .001); four (hsa-let-7a-5p, hsa-miR-25-3p, hsa-miR-126-3p, hsa-miR-320c) more than five-fold (P < .001); two (hsa-miR-342-3p and hsa-miR-320d) more than two-fold (P < .05); and two (hsa-miR-328-3p and hsa-miR-320e) more than two-fold (P > .05). Specifically, hsa-miR-22-3p increased 14.6-fold; hsa-miR-223-3p increased 13.0-fold; and hsa-miR-21-5p increased 12.0-fold. Based on bioinformatics functional analysis, target genes of top nine microRNAs (hsa-miR-22-3p, hsa-miR-223-3p, hsa-miR-21-5p, hsa-miR-23a-3p, hsa-miR-320b, hsa-let-7a-5p, hsa-miR-25-3p, hsa-miR-126-3p, and hsa-miR-320c) were annotated with positive regulation of cell proliferation and nervous system development, and mainly enriched in regulating pluripotency of stem cells signaling pathway, prolactin signaling pathway, and FoxO signaling pathway, etc. The prolactin, FoxO, ErbB, and TNF signaling pathway were relevant to immunomodulation. In particular, hsa-miR-22-3p expression was the most different during storage, with a fold change of 14.6, which might be a key mediator.

What is the context? Platelet transfusion is a widely used clinical treatment, but it is not totally safe. Side effects may happen to patients who receive the "older" platelet products. Exosomes in platelet products can be transfused to patients while receiving blood. Exosomes are accumulated in platelet products during storage. MicroRNAs are one of the important cargoes in exosomes, which can be delivered to the target cells, thus affecting their functions.This study aims to investigate and analyze the differential expression profiling of exosomal microRNAs in apheresis platelet concentrates during storage, and predict the potential function of the target genes. We found out the top nine differentially expressed microRNAs got involved in positive regulation of cell proliferation and nervous system development, and mainly enriched in regulating pluripotency of stem cells signaling pathway, prolactin signaling pathway, and FoxO signaling pathway, etc.What's new? Our study is the first one to test the exosomal microRNAs in the apheresis platelet concentrates. The apheresis platelet concentrates were stored for 1 day and 5 days. Compared the two time points, we obtained the differential expression profiling of exosomal microRNAs. Based on bioinformatics analyses and qRT-PCR results, we provided nine up-regulated microRNAs which might be critical mediators to communicate with target cells after transfusing.What's the impact? This study expands our knowledge of exosomal microRNA expression profiling from apheresis platelet concentrates along different storage periods. This might be relevant to immunomodulation in post transfusion situations.

Discovery and Synthesis of Amino Acids Modified Deoxycholic Acid Derivatives and in Vitro Antiproliferative Evaluation.

A series of deoxycholic acid (DCA) derivatives bearing amino acid moiety has been synthesized and investigated for their potential antiproliferative activities. DCA derivative compounds were synthesized by a two or three step synthetic approach. Their bioactivities were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and Western blotting analysis on three tumor cell lines A549 (human lung cancer cell line), MCF-7 (human breast cancer cell line) and HeLa (human cervical carcinoma cell). The novel derivatives DCA3d, DCA5a, DCA5b, DCA5c, and DCA5d were found to be promising antiproliferative agents. Furthermore, DCA5b showed the greatest cytotoxic activity by induction of apoptosis. These compounds show potentiality for further optimization as antitumor drugs.